Liu Y Q, Wang T P, Yan C W, Zhu M, Yang M, Wang M Y, Hu Z B, Shen H B, Jin G F
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Basic Research Center, Shandong Provincial Cancer Research Institute, Ji'nan 250117, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2021 Jun 10;42(6):1092-1096. doi: 10.3760/cma.j.cn112338-20201103-01303.
To explore the association between polygenic risk score (PRS) and age at onset and early-onset risk of gastric cancer (GC). Gastric cancer cases from existing genome-wide association study were included, and 112 single nucleotide polymorphisms associated with GC risk were used to derive individual PRS. Analysis of variance and Pearson correlation test was used to depict the relationship between PRS and GC onset age. Cases diagnosed before 50 years old were defined as early-onset gastric cancer. Cox proportional hazard model was used to test the association between PRS and early-onset GC risk with early-onset age as the timescale and low genetic risk (PRS ≤20%) as the reference group. A total of 8 629 cases, including 6 284 males (72.82%) and 2 345 females (27.18%), were included, and the mean age was (60.61±10.80) years old. The PRS was negatively correlated with age of GC onset (=-0.05, <0.001). The mean age of gastric cancer cases with low, intermediate, and high genetic risk were (61.68±10.33), (60.53±10.79), (59.80±11.20), respectively. PRS was significantly associated with the risk of early-onset GC in a dose-response manner (intermediate genetic risk: =1.19, 95%: 1.03-1.39, =0.022; high genetic risk: =1.44, 95%: 1.20-1.71, <0.001). PRS may contribute to the risk of both GC and early-onset GC. PRS can be used as a measurable indicator for risk prediction for occurrence and early-onset of GC.
探索多基因风险评分（PRS）与胃癌（GC）发病年龄及早发风险之间的关联。纳入来自现有全基因组关联研究的胃癌病例，并使用112个与GC风险相关的单核苷酸多态性来计算个体PRS。采用方差分析和Pearson相关检验来描述PRS与GC发病年龄之间的关系。将50岁之前诊断的病例定义为早发性胃癌。以早发年龄为时间尺度，低遗传风险（PRS≤20%）为参照组，采用Cox比例风险模型来检验PRS与早发性GC风险之间的关联。共纳入8629例病例，其中男性6284例（72.82%），女性2345例（27.18%），平均年龄为（60.61±10.80）岁。PRS与GC发病年龄呈负相关（=-0.05，<0.001）。低、中、高遗传风险的胃癌病例平均年龄分别为（61.68±10.33）、（60.53±10.79）、（59.80±11.20）岁。PRS与早发性GC风险呈显著的剂量反应关系（中等遗传风险：=1.19，95%：1.03 - 1.39，=0.022；高遗传风险：=1.44，95%：1.20 - 1.71，<0.001）。PRS可能与GC及早发性GC的风险相关。PRS可作为GC发生及早发风险预测的一个可测量指标。
